NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding homer proteins

Guo N. Huang, David L. Huso, Samuel Bouyain, Jianchen Tu, Kelly A. McCorkell, Michael J. May, Yuwen Zhu, Michael Lutz, Samuel Lester Collins, Marlin Dehoff, Shin Kang, Katharine Whartenby, Jonathan Powell, Daniel Leahy, Paul F Worley

Research output: Contribution to journalArticle

Abstract

T cell receptor (TCR) and costimulatory receptor (CD28) signals cooperate in activating T cells, although understanding of how these pathways are themselves regulated is incomplete. We found that Homer2 and Homer3, members of the Homer family of cytoplasmic scaffolding proteins, are negative regulators of T cell activation. This is achieved through binding of nuclear factor of activated T cells (NFAT) and by competing with calcineurin. Homer-NFAT binding was also antagonized by active serine-threonine kinase AKT, thereby enhancing TCR signaling via calcineurin-dependent dephosphorylation of NFAT. This corresponded with changes in cytokine expression and an increase in effector-memory T cell populations in Homer-deficient mice, which also developed autoimmune-like pathology. These results demonstrate a further means by which costimulatory signals are regulated to control self-reactivity.

Original languageEnglish (US)
Pages (from-to)476-481
Number of pages6
JournalScience
Volume319
Issue number5862
DOIs
StatePublished - Jan 25 2008

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NFATC Transcription Factors
Calcineurin
T-Lymphocytes
Costimulatory and Inhibitory T-Cell Receptors
Protein-Serine-Threonine Kinases
T-Cell Antigen Receptor
Pathology
Cytokines
Population
Homer Scaffolding Proteins
Proteins

ASJC Scopus subject areas

  • General

Cite this

Huang, G. N., Huso, D. L., Bouyain, S., Tu, J., McCorkell, K. A., May, M. J., ... Worley, P. F. (2008). NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding homer proteins. Science, 319(5862), 476-481. https://doi.org/10.1126/science.1151227

NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding homer proteins. / Huang, Guo N.; Huso, David L.; Bouyain, Samuel; Tu, Jianchen; McCorkell, Kelly A.; May, Michael J.; Zhu, Yuwen; Lutz, Michael; Collins, Samuel Lester; Dehoff, Marlin; Kang, Shin; Whartenby, Katharine; Powell, Jonathan; Leahy, Daniel; Worley, Paul F.

In: Science, Vol. 319, No. 5862, 25.01.2008, p. 476-481.

Research output: Contribution to journalArticle

Huang, GN, Huso, DL, Bouyain, S, Tu, J, McCorkell, KA, May, MJ, Zhu, Y, Lutz, M, Collins, SL, Dehoff, M, Kang, S, Whartenby, K, Powell, J, Leahy, D & Worley, PF 2008, 'NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding homer proteins', Science, vol. 319, no. 5862, pp. 476-481. https://doi.org/10.1126/science.1151227
Huang GN, Huso DL, Bouyain S, Tu J, McCorkell KA, May MJ et al. NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding homer proteins. Science. 2008 Jan 25;319(5862):476-481. https://doi.org/10.1126/science.1151227
Huang, Guo N. ; Huso, David L. ; Bouyain, Samuel ; Tu, Jianchen ; McCorkell, Kelly A. ; May, Michael J. ; Zhu, Yuwen ; Lutz, Michael ; Collins, Samuel Lester ; Dehoff, Marlin ; Kang, Shin ; Whartenby, Katharine ; Powell, Jonathan ; Leahy, Daniel ; Worley, Paul F. / NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding homer proteins. In: Science. 2008 ; Vol. 319, No. 5862. pp. 476-481.
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